Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Reaggregation of young cumulus cells with young or old nude oocytes partly restores soma-germline communication (143183)

Benjamin S Wu 1 2 , Daniel R Xing 1 2 , Nicola J Byers 1 3 , Bettina P Mihalas 1 , Kaushiki Kadam 1 , Irene E Sucquart 1 , Lindsay E Wu 2 , Robert B Gilchrist 1
  1. Discipline of Women’s Health, School of Clinical Medicine, UNSW Sydney, NSW, Australia
  2. School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, Australia
  3. School of Biomedical Engineering, UNSW Sydney, Sydney, NSW, Australia

Background:

Age-related female infertility is driven by declining oocyte quality. Oocytes are surrounded by cumulus cells (CCs) forming a cumulus-oocyte complex (COC). CCs enable oocyte development by transporting nutrients via transzonal projections (TZPs)(1). Whether CC ageing impacts oocyte ageing and quality is poorly understood. We aim to test whether soma-germline communication can be re-established by reaggregation of CCs and oocytes, including using age-mismatched CCs.

Methods:

Cumulus cells and denuded oocytes (DOs) or naked oocytes (NOs) from young (4-8 weeks) or old (52-58 weeks) hyperstimulated/unstimulated outbred Swisstac mice underwent an age-matched or -mismatched reaggregation protocol over 24-48 hours of pre-in vitro maturation (pre-IVM). TZPs were quantified via immunocytochemistry. Reaggregated COCs also underwent IVF.

Results:

TZP density was partly restored in age-matched and age-mismatched reaggregations (young CCs/old NOs, old CCs/young NOs, young CCs/young NOs) vs respective young or old non-reaggregated NO controls (all p<0.001). Prevention of precocious meiotic maturation during pre-IVM culture, intended to facilitate oocyte development, trended higher in young CC/old NO reaggregations versus old non-reaggregated NOs (p=0.08), while in age-matched young CC/young NO reaggregations there was no difference versus young non-reaggregated oocytes. Using an in vitro meiotic ageing model, blinded assessment of meiotic spindle morphology was improved for age-matched young CC/DO (p<0.01) and CC/NO (p<0.05) reaggregations, and chromosomal alignment for young CC/DO (p<0.05) but not CC/NO (p=0.32) reaggregations, versus respective nude oocyte controls. After IVF, age-matched young CC/DO and CC/NO reaggregations showed no change in 2-cell rate, while blastocyst formation rate was significantly improved by reaggregation of CC/DO (p=0.02) but not CC/NO, versus non-reaggregated nude oocyte controls.

Conclusion:

Overall, reaggregation partly restored multiple aspects of oocyte-CC communication, providing proof of concept for investigating if reaggregation with young CCs can improve old oocyte quality.

  1. Russell DL, Gilchrist RB, Brown HM, Thompson JG. Bidirectional communication between cumulus cells and the oocyte: old hands and new players?. Theriogenology. 2016 Jul 1;86(1):62-8.